Individually, both THC and anandamide cause vasorelaxation in rat mesenteric arteries. However, the interactions between exogenous and endogenous cannabinoids are still largely unknown, and evidence suggests that THC may act as an antagonist to other cannabinoid molecules (Bayewitch et al., 1996; Kelley & Thayer, 2004). We have therefore examined the effects of THC on vasorelaxation to anandamide.

Male Wistar rats (200-300 g) were killed by cervical dislocation. Small mesenteric resistance arteries (G3) or the superior mesenteric artery (G0) were isolated, cut into 2 mm lengths and mounted on a Mulvany-Halpern myograph. Vessels were bathed in oxygenated Krebs’ solution at 37oC. Vessels were set to a baseline tone of 5 mN, and U46619 was added to increase tension by at least 5 mN.

In summary, THC inhibits the vasorelaxant activities of the endogenous cannabinoid anandamide in small isolated mesenteric arteries. This is not through non-specific actions, or actions at the vanilloid receptor or CB1 receptor, but possibly through inhibition of EDHF activity via inhibition of intercellular communication.